ICD10 Code = C41.9
Genomic coordinate (human 13:48,303,751 RB1).
Cytoband (human 13q14.2 RB1).
OMIM’ genes @ 13q14.2 = 18 genes.
ClinVar = 4,764 RB1 variants reported.
PANTHER Classification of RB1 is PC00264 “transcription factor”.
Swallowtail chromosome-13 is 308 genes.
Cytoband Structures: WCWCCWG6BGBGB2GB2
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Here I 🎁 present: “Somatic Osteosarcoma“, Victor McKusick, Mendelian Inheritance in Man’, 1966. (RB1)
INTRODUCTION.
The RB1-E2F pathway acts as the primary gatekeeper of the mammalian cell cycle, specifically controlling the critical transition from the G1 phase (growth) to the S phase (DNA replication).
When this molecular “switch” is broken or lost, it triggers the genomic instability and uncontrolled proliferation modeled in the ABOVE cusp catastrophe diagram.
The Active Off-State: Suppression of Cell Division.
In a normal, non-dividing, or resting cell (G0/early G1 phase), the RB1 gene product (pRB) acts as a tumor suppressor by putting the brakes on cell division.
The Hypophosphorylated State: pRB is in a low-phosphorylation (hypophosphorylated) state, meaning it is active and tightly folded.
Binding E2F: Active pRB physically binds to E2F transcription factors (specifically activator E2Fs like E2F1, E2F2, and E2F3).
Transcriptional Silencing: By grabbing onto E2F, pRB physically blocks E2F from binding to DNA. Furthermore, pRB recruits chromatin-remodeling enzymes (like histone deacetylases) to silence the target genes. As a result, the cell cannot progress to DNA replication.
